Ignite Creation Date:
2025-12-24 @ 5:37 PM
Ignite Modification Date:
2026-01-11 @ 2:29 AM
Study NCT ID:
NCT07246668
Status:
RECRUITING
Last Update Posted:
2025-11-24
First Post:
2025-11-17
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Phase II Single-Arm Clinical Study to Evaluate the Efficacy and Safety of Carbon Ion Radiotherapy With Atezolizumab and Bevacizumab Combination Therapy in Patients With Advanced Hepatocellular Carcinoma
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006528', 'term': 'Carcinoma, Hepatocellular'}, {'id': 'D008113', 'term': 'Liver Neoplasms'}, {'id': 'D002277', 'term': 'Carcinoma'}], 'ancestors': [{'id': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D004067', 'term': 'Digestive System Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D008107', 'term': 'Liver Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'This is an open-label study; no masking will be applied.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'This study is designed as a single-group, open-label, prospective phase II trial evaluating the combination of carbon ion radiotherapy with atezolizumab plus bevacizumab for advanced hepatocellular carcinoma.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 52}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-03-10', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-11', 'completionDateStruct': {'date': '2028-03', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-11-17', 'studyFirstSubmitDate': '2025-11-17', 'studyFirstSubmitQcDate': '2025-11-17', 'lastUpdatePostDateStruct': {'date': '2025-11-24', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2025-11-24', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2027-03', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Progression-Free Survival (PFS)', 'timeFrame': 'Three years', 'description': 'Progression-free survival is defined as the time from the first administration of atezolizumab plus bevacizumab to the date of documented tumor progression or death from any cause, whichever occurs first.'}], 'secondaryOutcomes': [{'measure': 'Overall survival', 'timeFrame': 'Three years', 'description': 'Overall survival is defined as the time from the first administration of atezolizumab plus bevacizumab to death from any cause.\n\nSurviving patients will be censored at the date of the last follow-up. OS defines death or last follow-up date from the date of first AtezoBev administration.'}, {'measure': 'intrahepatic tumor response', 'timeFrame': 'Three years', 'description': 'Tumor response will be evaluated according to RECIST criteria at predefined time points.\n\nComplete Response (CR): Disappearance of all target lesions Partial Response (PR): ≥30% decrease in the sum of the longest diameters of target lesions Progressive Disease (PD): ≥20% increase in the sum of the longest diameters of target lesions, or appearance of new lesions Stable Disease (SD): Does not meet criteria for CR, PR, or PD Disease Control Rate (DCR) will be measured as CR + PR + SD. (ORR = CR + PR / DCR = CR + PR + SD)'}, {'measure': 'rate of achieving curative down-staging', 'timeFrame': 'Three years', 'description': 'The proportion of patients who become eligible for curative-intent treatments after tumor down-staging will be assessed.\n\nCurative treatments may include liver transplantation, hepatic resection, ablation, TACE, or TARE, based on the discretion of the treating physician. How often radical treatments become possible after down-staging A decrease in stage was confirmed during the course of treatment, and treatment targeting the root, such as liver transplantation, hepatic resection, other local ablation, TACE, or TARE, is allowed at the discretion of the physician.'}, {'measure': 'treatment-related toxicity', 'timeFrame': 'Three years', 'description': "Treatment-related adverse events will be evaluated and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).\n\nSafety follow-up will continue from study entry until 30 days after the final planned dose of protocol treatment, or until initiation of subsequent alternative therapy, whichever occurs first.Toxicity is assessed using the National Cancer Society's Common Criteria for Judgment (NCI-CTC). Patients participating in the treatment are subject to safety and toxicity follow-up from participation in the study to 30 days after the final dose of the treatment under the plan is completed (or until the earliest of the start of the next alternative treatment)."}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Hepatocellular Carcinoma', 'Liver Neoplasms', 'Carcinoma', 'Hepatocellular']}, 'descriptionModule': {'briefSummary': 'This single-center, prospective phase II clinical trial evaluates the safety and therapeutic efficacy of combining carbon ion radiotherapy with the standard first-line regimen of atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma. The study aims to determine whether the addition of carbon ion radiotherapy enhances tumor control and improves clinical outcomes beyond those achieved with systemic therapy alone. Key endpoints include overall survival, progression-free survival, objective response rate, and treatment-related adverse events.', 'detailedDescription': 'This clinical trial aims to determine whether adding carbon ion radiotherapy to atezolizumab-bevacizumab therapy improves tumor control and enhances immune response in patients with advanced hepatocellular carcinoma. Over a 3-year study period, eligible patients receiving atezolizumab and bevacizumab who are also suitable for carbon ion radiotherapy will undergo the combined treatment. Clinical outcomes including survival, progression, radiologic response, and toxicity (graded using CTCAE v5.0) will be monitored and assessed.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '20 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age ≥ 18 years Histologically or radiologically confirmed hepatocellular carcinoma (HCC) Barcelona Clinic Liver Cancer (BCLC) stage B or C, not eligible for curative surgery or transplantation.\n\nAt least one measurable lesion according to RECIST criteria. Eligible for treatment with atezolizumab plus bevacizumab based on clinical judgment.\n\nCandidate for carbon ion radiotherapy determined by radiation oncologist. Child-Pugh class A liver function Eastern Cooperative Oncology Group (ECOG) performance status 0-1\n\nAdequate organ and marrow function, including:\n\nAbsolute neutrophil count ≥ 1,500/μL Platelet count ≥ 75,000/μL Hemoglobin ≥ 8.5 g/dL Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min AST/ALT ≤ 5 × ULN Total bilirubin ≤ 3 mg/dL No uncontrolled esophageal or gastric varices, confirmed by endoscopy (within 6 months), or adequately treated before enrollment.\n\nAbility to understand and willingness to sign a written informed consent form.\n\nExclusion Criteria:\n\n* Prior systemic therapy with anti-PD-1, anti-PD-L1, or anti-VEGF agents within the past year.\n\nPrior carbon ion radiotherapy to the same anatomical region.\n\nPresence of uncontrolled or severe cardiovascular disease, including:\n\nRecent myocardial infarction (within 6 months) Uncontrolled hypertension NYHA class III-IV heart failure Active or history of autoimmune disease requiring systemic immunosuppressive therapy.\n\nActive infection, including:\n\nUncontrolled bacterial, viral, or fungal infection Active tuberculosis HIV infection, or active hepatitis B/C with uncontrolled viral replication.\n\nSignificant bleeding risk, including:\n\nActive gastrointestinal bleeding Untreated or high-risk varices Coagulopathy not controllable with standard therapy Portal vein tumor thrombosis (PVTT) of grade Vp4 if judged unsuitable for treatment by investigator.\n\nPregnant or breastfeeding women History of organ transplantation, including liver transplantation. Any condition judged by the investigator to interfere with study participation, treatment compliance, or safety evaluation.'}, 'identificationModule': {'nctId': 'NCT07246668', 'briefTitle': 'A Phase II Single-Arm Clinical Study to Evaluate the Efficacy and Safety of Carbon Ion Radiotherapy With Atezolizumab and Bevacizumab Combination Therapy in Patients With Advanced Hepatocellular Carcinoma', 'organization': {'class': 'OTHER', 'fullName': 'Yonsei University'}, 'officialTitle': 'A Phase II Single-Arm Clinical Study to Evaluate the Efficacy and Safety of Carbon Ion Radiotherapy With Atezolizumab and Bevacizumab Combination Therapy in Patients With Advanced Hepatocellular Carcinoma', 'orgStudyIdInfo': {'id': '4-2025-0048'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Carbon Ion Radiotherapy + Atezolizumab + Bevacizumab', 'description': 'Participants will receive standard first-line systemic therapy with atezolizumab (1200 mg IV every 3 weeks) plus bevacizumab (15 mg/kg IV every 3 weeks). Carbon ion radiotherapy will be integrated as a sequential local treatment during the early phase of systemic therapy.\n\nCarbon ion radiotherapy will be delivered to the primary hepatic tumor using a hypofractionated regimen (approximately 4-12 fractions), with dose and fractionation individualized according to tumor extent, anatomical proximity to gastrointestinal organs, and institutional organ-at-risk constraints.\n\nFollowing completion of carbon ion radiotherapy, participants will continue atezolizumab-bevacizumab maintenance therapy until radiologic disease progression, unacceptable toxicity, or withdrawal of consent. This protocol is designed to enhance local tumor control while preserving the systemic therapeutic benefit of atezolizumab and bevacizumab.', 'interventionNames': ['Radiation: Carbon Ion Radiotherapy Atezolizumab Bevacizumab']}], 'interventions': [{'name': 'Carbon Ion Radiotherapy Atezolizumab Bevacizumab', 'type': 'RADIATION', 'otherNames': ['Atezolizumab: Anti-PD-L1 antibody Bevacizumab: Anti-VEGF monoclonal antibody Carbon Ion Radiotherapy: Heavy-ion radiotherapy, C-ion RT'], 'description': 'Participants will initiate systemic therapy with atezolizumab (1200 mg IV every 3 weeks) and bevacizumab (15 mg/kg IV every 3 weeks). Carbon ion radiotherapy will subsequently be administered to the primary hepatic lesion during the early phase of systemic therapy.\n\nCarbon ion radiotherapy will be delivered using a hypofractionated schedule (approximately 4-12 fractions), with dose and fractionation individualized based on tumor size, anatomical location, and organ-at-risk considerations. After completion of carbon ion radiotherapy, participants will continue maintenance treatment with atezolizumab and bevacizumab until disease progression or unacceptable toxicity.', 'armGroupLabels': ['Carbon Ion Radiotherapy + Atezolizumab + Bevacizumab']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Seoul', 'status': 'RECRUITING', 'country': 'South Korea', 'contacts': [{'name': 'Ik Jae Lee', 'role': 'CONTACT', 'email': 'IKJAE412@YUHS.AC', 'phone': '+82-2-2228-8117'}], 'facility': 'Yonsei University Health System, Severance Hospital', 'geoPoint': {'lat': 37.566, 'lon': 126.9784}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Yonsei University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}